The objectives of this proposal are to investigate the role of gastrointestinal hormones (GIH) in the digestive (and related) processes. We will study the mechanisms for release of neurotensin (NT) from the gut and from medullary carcinoma of the thyroid. We will determine the effect of NT on gastric secretion stimulated by different routes. We plan to characterize cholecystokinin (CCK), NT, bombesin, and peptide YY (PYY) by HPLC. We will determine the differential hepatic uptake of different molecular forms of endogenously released CCK by bioassay and radioimmunoassay. We plan to study the mechanisms of actions of CCK on gallbladder (GB) smooth muscle. We will study the action of PYY on gastric secretion and measure PYY receptors in antrum and fundus. We plan to study the mechanism of relaxation of the sphincter of Oddi by CCK and to determine, by receptor studies, whether substance P is involved. We will determine the relationships between the gut and pancreatic acinus and note particularly the roles of NT, prostaglandins, and indomethacin. We will use whole animals, isolated pancreas, and dispersed acini. We plan to characterize the enterinsulinar relationships of GIH and calcium-regulatory peptides on secretion of insulin and glucagon, to determine whether intracerebroventricular administration of GI and calcium-regulatory peptides influence secretion of insulin and glucagon, and to examine the influence of pregnancy on the relationship between gut hormones and pancreatic endocrine hormone secretion. We will study the role of GIH in the inhibition and stimulation of growth of the pancreas and the relationship with hormone receptors and efficacy of action. We will study the role of stimulatory and inhibitory peptides in the pathogenesis and course of experimental acute pancreatitis. We plan to determine the effects of GIH on the stimulation and inhibition of growth of cancers of the gut and pancreas. We will measure GIH receptors in gut and pancreatic cancer cells. We plan clinical studies on the relationship between GIH and chronic pancreatitis in patients before and after operation. We will continue our metabolic studies on patients with the Zollinger-Ellison syndrome (ZES) and plan to compare nutrition after total gastrectomy in ZES and non-ZES patients. We will study the role of GIH in patients with thryoid disease. We will study the metabolism of NT in man. We will determine the effects of various stages of pregnancy, as compared with the postpartum state, on the relationship between CCK and GB contraction in women.